Cell-Mediated Immunity after Bacterial Infection of the Lower Respiratory Tract

Cantey, J. Robert; Hand, W. Lee; Hughes, Carl G.; Lund, Mary E.; King, Neva L.

doi:10.1172/jci107856

Cited by 40 publications

(16 citation statements)

References 43 publications

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“…Previous investigations have examined the response to lymphokines of animal macrophages. Lymphokine (or cytokine)-treated animal alveolar macrophages have been shown to have altered adherence, migration, or aggregation, and increased anti-microbial activity against Nocardia asteroides and Listeria monocytogenes (19)(20)(21)(22)(23). Studies with human macrophages may be more relevant to human immunity than studies with animal macrophages because of interspecies differences in macrophage effector functions (24).…”

Section: Resultsmentioning

confidence: 99%

Interaction between the legionnaires' disease bacterium (Legionella pneumophila) and human alveolar macrophages. Influence of antibody, lymphokines, and hydrocortisone.

Nash¹,

Libby²,

Horwitz³

1984

J. Clin. Invest.

241

165

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Abstract. We have studied the interaction between virulent Legionella pneumophila and human alveolar macrophages, the resident phagocytes at the site of infection in Legionnaires' disease. L. pneumophila multiplied 2.5-5 logs within 3 d, as measured by colony forming units, when incubated with freshly explanted alveolar macrophages in monolayer culture. At the peak of bacterial multiplication, the alveolar macrophage monolayers were destroyed. L. pneumophila multiplied more rapidly in 4-d-old than in freshly explanted alveolar macrophages. Inside alveolar macrophages, L. pneumophila were located within membrane-bound vacuoles whose cytoplasmic sides were studded with ribosomes.Alveolar macrophages that were incubated with concanavalin A (Con A) stimulated human mononuclear cell supernatants (cytokines), inhibited L. pneumophila multiplication, and the degree of inhibition was proportional to the concentration of Con A supernatant added.Anti-L. pneumophila antibody in conjunction with complement promoted phagocytosis of L. pneumophila by alveolar macrophages. By electron microscopy, most (75%) of the phagocytized L. pneumophila were intracellular. However, freshly explanted alveolar macroThis work was presented in part at the

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Section: Resultsmentioning

confidence: 99%

Interaction between the legionnaires' disease bacterium (Legionella pneumophila) and human alveolar macrophages. Influence of antibody, lymphokines, and hydrocortisone.

Nash¹,

Libby²,

Horwitz³

1984

J. Clin. Invest.

241

165

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“…could be demonstrated, lavage was performed in an uninvolved lung segment. Total and differential cell counts and viability determinations were performed as previously described (1,16 (6,7,14 exclusion. Uptake of antibiotics by AM.…”

mentioning

confidence: 99%

Antibiotic uptake by alveolar macrophages of smokers

Hand¹,

Boozer²,

King-Thompson³

1985

Antimicrob Agents Chemother

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Cigarette smoking, particularly when associated with chronic pulmonary disease, increases the risk of respiratory tract infection. Thus, we elevated the uptake of antibiotics by alveolar macrophages (AM) obtained by bronchoalveolar lavage from persons who smoke and have associated pulmonary abnormalities, circumstances which adversely affect certain macrophage functions. The entry of radiolabeled drugs into AM was determined by a velocity-gradient centrifugation technique, and uptake was expressed as the ratio of cellular to extracellular antibiotic concentration (C/E). Cefamandole and penicillin G were taken up poorly by the AM obtained from smokers (C/E c 1). Cellular levels of isoniazid, gentamicin, and tetracycline were similar to their extracellular concentrations. The lipid-soluble drugs lincomycin, chloramphenicol, and rifampin were concentrated severalfold by the AM from smokers (C/E = 3 to 11). Ethambutol also entered macrophages readily (C/E = 11). Erythromycin and clindamycin were massively concentrated by the AM from smokers (C/E = 23 to 56). The AM of smokers accumulated a lipid-soluble antibiotic (rifampin) and actively transported agents (erythromycin propionate, clindamycin) more avidly than did the AM of nonsmoker$. Augmented uptake of these antibiotics by the AM of smokers may be related to structural and functional alterations induced by smoking.People who smoke cigarettes, especially those with asso-

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“…Cells were collected from the lower respiratory tract of New Zealand rabbits by saline lavage, as previously described (7,17 Radiolabeled substances in various concentrations (as noted below) were added to the macrophage suspensions. The mixtures were incubated at 37°C in 95% air-5% CO2.…”

Section: Methodsmentioning

confidence: 99%

Membrane transport of clindamycin in alveolar macrophages

Hand¹,

King-Thompson²

1982

Antimicrob Agents Chemother

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The use of antibiotics which can penetrate phagocytic cells and kill intracellular organisms is desirable in the treatment of chronic facultative bacterial infections. Recently, we reported that several antibiotics were selectively concentrated by rabbit alveolar macrophages. Clindamycin accumulation was especially marked. In the present study we evaluated the plasma membrane transport (initial uptake) of clindamycin in alveolar macrophages. The transport of clindamycin is an active process, as documented by requirements for cellular viability, elevated environmental temperature, metabolic energy, and establishment of the 40- to 50-fold cellular/extracellular gradient. Energy for membrane transport of the drug depended at least in part upon mitochondrial oxidative respiration and cell membrane Na-K pump activity. Kinetic analysis of active clindamycin transport revealed it to be saturable, with a high binding affinity (Km = 1 mM) and a high velocity of uptake (Vmax = 15.8 nmol/45 s per 10(6) cells). Clindamycin uptake was not influenced by the presence of hexose or amino acids, but was inhibited by nucleosides (adenosine, puromycin). Decreased clindamycin transport in the presence of puromycin was typical of competitive inhibition (increased Km, unchanged Vmax). Conversely, competitive inhibition of adenosine transport by clindamycin was documented. Thus, clindamycin is transported into alveolar macrophages via the nucleoside system. The potential biological consequences of this unique antibiotic transport mechanism are of interest.

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Cell-Mediated Immunity after Bacterial Infection of the Lower Respiratory Tract

Cited by 40 publications

References 43 publications

Interaction between the legionnaires' disease bacterium (Legionella pneumophila) and human alveolar macrophages. Influence of antibody, lymphokines, and hydrocortisone.

Interaction between the legionnaires' disease bacterium (Legionella pneumophila) and human alveolar macrophages. Influence of antibody, lymphokines, and hydrocortisone.

Antibiotic uptake by alveolar macrophages of smokers

Membrane transport of clindamycin in alveolar macrophages

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